Protein tyrosine kinases often play important roles in signal transduction leading to cellular proliferation. The large family of protein tyrosine kinases includes many growth factor receptors. See, e.g., Pawson, et al. (1990) Trends in Genetics 6:350-356. Growth factor receptors are important in control and regulation of cellular physiology and development. Although these receptors have been found on various cell lineages, their specific roles in regulation of development of different cell lineages are generally poorly understood. Suggestions of a role for a protein tyrosine kinase in hematopoiesis have been largely based upon the identification of the c-kit receptor tyrosine kinase as the W locus, mutations in which affect erythroid and mast cell lineages. See, e.g., Chabot, et al. (1988) Nature 335:88-89; and Geissler, et al. (1988) Cell 55:185-192.
Besides the gene product of the W locus, another protein tyrosine kinase had been isolated and characterized. See Matthews, et al. (1991) Cell 65:1143-1152; and Rosnet, et al. (1991) Oncogene 6:1641-1650. This protein has been designated Fms-like tyrosine kinase 3 (Flt3) or Flk2. Although it has been localized to particular cell types, e.g., placenta, gonad, neural, and hematopoietic, its biological effects on cell differentiation and physiology have not been fully described.
Moreover, the receptor should mediate cellular signal transduction in response to a natural ligand. The nature of the ligand has yet to be identified, and its physiological effects and cell lineage specificity remain undescribed. However, the distribution of the receptor suggests that the ligand has a role in regulating cell physiology and development in a multiplicity of cell lineages.
The absence of knowledge about the structural, biological, and physiological properties of the regulatory factors which naturally bind to the Flt3 tyrosine kinase receptor prevents the modulation of the effects of the factors. Medical conditions where regulation of the development or physiology of relevant cells thus remain unmanageable. However, the present invention provides solutions to these and many other problems.